Microfluidic dissociation and clearance of Alzheimer's beta-amyloid aggregates

Abstract

The abnormal aggregation of beta-amyloid peptide (A beta) in the brain is a major histopathological feature of Alzheimer's disease. Herein, we first report on microfluidic dissociation and clearance analysis of preformed A beta aggregates for parallel screening of aggregate destabilizers. As a proof of the concept for the microfluidic platform, we investigated (1) microfluidics-based clearance of metal ion-induced A beta aggregates using different types of metal chelators, (2) the clearance effect of deferoxamine on A beta aggregates within microchannels, (3) comparison between destabilized A beta dissociated from pre-formed A beta aggregates and remaining deposits within the microchannels both before and after the clearance, and (4) secondary structure change in A beta deposits by the clearance treatment. The microfluidics-based clearance system should be suitable for efficient screening of chemical candidates to enhance the clearance of A beta deposits prior to their in vivo evaluation. (C) 2010 Elsevier Ltd. All rights reserved.